PATHOLOGY OF INTERVERTEBRAL DISC DISEASE

椎间盘疾病的病理学

• 批准号: 3792207
• 负责人: ROLAND W MOSKOWITZ
• 金额: --
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3792207
• 关键词: biological models; biomechanics; chondrocytes; crosslink; fluorescent dye /probe; glycosylation; high performance liquid chromatography; histopathology; human tissue; image processing; intervertebral disk; laboratory rat; mechanical stress; microradiography; pathologic bone resorption; pathologic process; proteoglycan; spinal cord imaging /visualization; spine disorder

Although intervertebral disc degeneration is a leading cause of musculoskeletal disability leading to pain, work loss and high cost to industry, a clear understanding of mechanisms of disease pathogenesis and specific therapeutic approaches is still lacking. Few studies have been directed toward parallel and sequential assessment of biochemical, biomechanical and anatomic responses. The proposed investigations in a well-defined model are designed to utilize biochemical, biomechanical, histopathologic and histomorphometric methods to define the pathophysiologic processes taking place during intervertebral disc degeneration. The specific objectives of the studies are designed to 1) determine whether biochemical and physicochemical changes in the intervertebral disc and vertebral bodies precede or follow alterations in joint biomechanics and structure. Correlative studies will utilize measurements of disc hydration and swelling pressure responses to assess physicochemical changes; and fixed charge density (FCD) measurements to assess proteoglycan alterations. Biomechanical assessment of disc alterations will be evaluated utilizing measurements of disc responses in bending and compression modes. 2) determine whether subchondral bone responses precede and initiate/contribute to alterations in the intervertebral disc. This question will be investigated utilizing both sequential fluorochrome labeling, and quantitative measurements of subchondral bone responses utilizing an automated image analysis system (Bioquant IV). 3) determine whether alterations in collagen cross-linking and/or non-enzymatic glycosylation play a major role in the disc degenerative process. In addition to assessing de novo responses of these biochemical parameters, the effect of variations in biomechanical stresses on the rate and degree of these responses will be investigated.

尽管椎间盘退变是导致腰椎间盘突出的主要原因 肌肉骨骼残疾导致疼痛、工作损失和高昂的成本 工业方面，对疾病的发病机制和发病机制有清晰的认识 目前仍缺乏具体的治疗方法。很少有研究是这样的 针对生化的并行和顺序评估， 生物力学和解剖学反应。拟议中的调查将在 定义良好的模型旨在利用生化、生物力学、 组织病理学和组织形态计量学方法确定 椎间盘病变过程中的病理生理过程 退化。研究的具体目标设计为1) 确定在生物化学和物理化学方面的变化 椎间盘和椎体在以下改变之前或之后 关节生物力学和结构。相关研究将利用 测量椎间盘水化和膨胀压力反应以评估 物理化学变化和固定电荷密度(FCD)测量 评估蛋白多糖的改变。腰椎间盘的生物力学评价 更改将使用以下各项中的磁盘响应测量进行评估 弯曲和压缩模式。2)确定软骨下骨是否 响应先于并启动/促成了 腰间盘。这个问题将利用两种方法进行调查 顺序荧光标记和定量测量 使用自动图像分析系统的软骨下骨反应 (BioQuant IV)。3)确定胶原蛋白是否发生了交联性改变 和/或非酶糖基化在视盘中起主要作用 退化过程。除了评估这些项目的从头开始反应之外 生物力学应力变化对生化参数的影响 将对这些反应的速度和程度进行调查。